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Perforation of the appendix in the neonatal period
Perforation of the Appendix in the N e o n a t a l Period By N. M. A. Bax, R. G. Pearse, N. Dommering, and J. C. Molenaar Rotterdam, The Netherlands 9 Perforation of the appendix in the neonatal period may be a complication of neonatal necrotizing enterocolitis and should be differentiated from perforating appendicitis in later life. A patient is presented together with a review of the literature to illustrate this concept. Perforation of the appendix occurred in a 12-day-old preterm baby. The cause of this perforation is assumed to be localized full thickness necrosis of the appendiceal wall, a form of neonatal necrotizing enterocolitis. The similarity b e t w e e n the clinical histories of neonates with so called "appendicitis" and those with necrotizing enterocolitis is pointed out. It is argued that "'idiopathic primary peritonitis" probably does not exist, but that the peritonitis may be secondary to similar small perforations of the bowel. The importance of a thorough search for such a perforation is stressed. INDEX W O R D S ; Neonatal appendicitis; neonatal necrotizing enterocolitis; idiopathic primary peritonitis; neonatal appendicular perforation.
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ERFORATION o f t h e a p p e n d i x is r a r e in t h e n e w b o r n p e r i o d in c o n t r a s t w i t h its o c c u r r e n c e in l a t e r c h i l d h o o d . In 1966 F o n k a l s rud ~ r e v i e w e d 172 cases of n e o n a t a l peritonitis. O f t h e s e 172 cases 79 h a d peritonitis on a basis o f g a s t r o i n t e s t i n a l p e r f o r a t i o n , b u t in not one p a t i e n t was t h e p e r f o r a t i o n l o c a l i z e d in the a p p e n d i x . I d i o p a t h i c p r i m a r y p e r i t o n i t i s was d i a g n o s e d in 9 p a t i e n t s . In 1969 L l o y d 2 w r o t e on t h e e t i o l o g y of g a s t r o i n t e s t i n a l p e r f o r a t i o n s in t h e n e w b o r n , r e v i e w i n g 402 cases. A g a i n no m e n t i o n was m a d e of t h e a p p e n d i x as a site of p e r f o r a t i o n , w h i l e in 25 p a t i e n t s t h e site o f perfor a t i o n was not d e t e r m i n e d . S c h a u p p 3 r e p o r t e d on n e o n a t a l " a p p e n d i c i t i s " in 1960, d e s c r i b i n g 5 cases of his o w n a n d r e v i e w i n g 19 o t h e r s f r o m t h e l i t e r a t u r e . S i n c e 1960, h o w e v e r , at least 20 n e w cases of so-called n e o n a t a l " a p p e n d i c i t i s "
From the Departments o f Pediatric Surgery and Pediatrics, Sophia Children's Hospital and Neonatal Unit, Erasmus University, Rotterdam, The Netherlands. Address reprint requests to N. M. A. Bax, University Hospital Rotterdam, Sophia Children's Hospital and Neonatal Unit, Gordelweg 160, 3038 GE Rotterdam, The Netherlands. 9 1980 by Grune & Stratton, Inc. 00 22-3468/80/150 2~)016501.00/0
200
h a v e b e e n a d d e d to t h e world l i t e r a t u r e 4-~6 s e e m ingly i n d i c a t i n g an i n c r e a s i n g i n c i d e n c e of this problem. CASE REPORT
A female child, weighing 2420 g, was delivered at 35 wk gestation from a 25-yr-old mother. Pregnancy had been uneventful until the membranes ruptured spontaneously 84 hr before birth. No problems were encountered during delivery and the Apgar score was 8 at 1 min and 10 at 5 min. On the fourth day, the serum total bilirubin rose to 235 #mole/1 for which she received phototherapy and extra fluids in a peripheral vein. On the seventh day she developed a temperature of 39.9~ and became clinically ill with bile-stained vomiting, constipation, abdominal distension, grunting respiration, and poor peripheral circulation. Blood culture and lumbar puncture were done at this time, but no bacteria were cultured and direct microscopy, total protein and glucose content of cerebrospinal fluid were normal. She was started on kanamycin and cephaloridin intravenously, but her condition did not improve. On the 12th day of life she was referred to the Sophia Children's Hospital, Rotterdam. On admission she was clearly septic and presented with erythema and edema of the skin of the right iliac fossa where a mass could be felt. A diagnosis of peritonitis possibly secondary to necrotizing enterocolitis or appendicitis was made. A plain abdominal x-ray showed free air in the peritoneal cavity and signs of ascites. At laparotomy, diffuse purulent peritonitis was found, but without obvious perforation. A careful search revealed a small, apparently superficial, defect at the tip of the appendix, which otherwise looked healthy. It was decided to perform an appendectomy. During ligation of the base of the appendix feces extruded through the defect, confirming the diagnosis of appendiceal perforation. Escherichia coli and bacteroides were cultured from the peritoneal cavity. Both were sensitive for carbenicillin and gentamycin, which she had received in combination since admission to our hospital. She recovered without complications and was discharged in good health. Hirschsprung's disease was excluded by mucosal biopsy. Histologic examiniation of the removed appendix revealed the presence of periappendicitis without signs of classical appendicitis. DISCUSSION
W e believe t r u e a p p e n d i c i t i s as seen in o l d e r c h i l d r e n to be an e x c e e d i n g l y r a r e o c c u r r e n c e in t h e n e w b o r n . T h e t e r m i n o l o g y in t h e l i t e r a t u r e t e n d s to be c o n f u s i n g as m o s t c a s e s o f p e r f o r a tion of t h e a p p e n d i x in the n e o n a t a l period a r e classed t o g e t h e r u n d e r t h e t e r m " a p p e n d i c i t i s . "
Journal of Pediatric Surgery, Vol. 15, No. 2 (April), 1980
NEONATAL PERFORATION OF THE APPENDIX
201
We feel that many of these cases of neonatal "appendicitis" are the result of localized ischemic full thickness necrosis, a form of neonatal necrotizing enterocolitis. Animal experiments, working on the concept of selective circulatory shut-down as an asphyxial defence mechanism (the so-called diving reflex), demonstrate that bowel-wall perfusion and especially mucosal perfusion is dramatically reduced in the stomach, distal ileum and colon during asphyxia. ~7 We strongly suspect that the appendix participates in this process. As stated by Touloukian, ~8 localized perforation without obvious surrounding necrosis can exist and represents a very well localized full thickness zone of necrosis, particularly if found in the ileum or colon (or in the appendix). This is not surprising as the intestine with neonatal necrotizing enterocolitis has a marked healing capacity. ~9 The time that elapsed between the onset of neonatal necrotizing enterocolitis and the clinical manifestations of a perforation may have been long enough for the healing of the rest of the bowel without full thickness necrosis, so that at laparotomy only a localized perforation is seen, the rest of the bowel looking quite normal. We have found only one case in the literature where perforation of the appendix could have been associated with proximal appendiceal obstruction. ~3 In contrast, a calcified appendicolith is found in about one-third of the patients with classic appendicitis beyond the neonatal period. H,~3 Obstructive disease of the colon, e.g., Hirschsprung's disease, has been implicated in the pathogenesis of perforation of the appendix in the neonatal period. 2~ According to La Place's Law, however, obstruction of the distal colon is more likely to result in perforation of the cecum than of the remaining colon or appendix if mechanical causes alone are to be considered. We believe that the perforation of the appendix in such cases is the result of the accompanying
enterocolitis and not directly due to the mechanical effects. Perforation of the appendix in the neonatal period while still very rare, is being reported with increasing frequency. At the same time there has been an increase in the frequency of neonatal necrotizing enterocolitis. 18 It is remarkable that factors that have been implicated in the etiology and the pathogenesis of neonatal necrotizing enterocolitis, such as prematurity, perinatal asphyxia, premature rupture of membranes and umbilical vessel catherization, are precisely those which have been reported in most of the cases of neonatal "appendicitis." The age of onset of the symptoms is also similar in both. Further support for the theory that neonatal "appendicitis" is a separate disease entity from appendicitis in later childhood, is the extreme rarity of reports of appendicitis in babies between the ages of one month and one year. Of the combined group of 72 patients with appendicitis under the age of 2 yr, reported by Barlett 11 and Grosfeld, 13 only 7 patients fell in the age group of between 1 and 12 mo and only 1 patient out of 30 patients reported by Fields 8 was under 3 yr of age. We feel therefore, that the case presented here and many of the cases of neonatal "appendicitis" reported in the literature, are examples of neonatal necrotizing enterocolitis. One of the three patients described by Grosfeld 13 had the typical changes of necrotizing enterocolitis of the cecum and appendix. Furthermore, we suggest that a similar process situated in the appendix or elsewhere in the bowel may lead to the so-called idiopathic primary peritonitis. We should like to stress the importance of a thorough search for such localized defects before closing the abdomen with this diagnosis. Failure to find and to deal with the site of perforation would explain the very high mortality reported in babies in whom idiopathic primary peritonitis has been diagnosed.
REFERENCES 1. Fonkalsrud EW, Ellis DG, Clatworthy HW: Neonatal peritonitis. J Pediatr Surg 1:227-239, 1966 2. Lloyd JR: The etiology of gastrointestinal perforations in the newborn. J Pediatr Surg 4:77-85, 1969 3. Schaupp W, Clausen EG, Ferrier PK: Appendicitis during the first month of life. Surgery 48:805-811, 1960
4. Hardman RP, Bowerman D: Appendicitis in the newborn. Am J Dis Child 105:99 101, 1963 5. Firror HV, Myers HAP: Perforating appendicitis in premature infants. Surgery 56:581-583, 1964 6. Neve R, Quenville NF: Appendicitis with perforation in a 12 day-old infant. Can Med Assoc J 94:447-448, 1966
202
7. Tabrinsky J, Westerfeld R, Cavanaugh J: Appendicitis in the newborn. Am J Dis Child 3:557 558, 1966 8. Fields IA, Cole NM: Acute appendicitis in infants thirty-six months of age or younger. Am J Surg 113:269275, 1967 9. Denes J, Gergely K, Mohacsi A, Leb J: Die frfihgeborenen-appendicitis. Z Kinderchir 5:400-406, 1968 10. Parsons JM, Miscall BG, McSherry CK: Appendicitis in the newborn infant. Surgery 67:841-843, 1969 11. Barlett RH, Eraklis A J, Wilkinson RH: Appendicitis in infancy. Surg Gynecol Obstet 130:99-104, 1970 12. Schellerer W, Schwemme K, Decker R: Perforierte Appendizitis bei einem FrUhgeborenen im Alter von 14 Tagen. Z Kinderchir 9:434-437, 1971 13. Grosfeld JL, Weinberger M, Clatworthy HW: Acute appendicitis in the first two years of life. J Pediatr Surg 8:285-293, 1973 14. Reuter G, Krause l: Beitrag zur Problematik der Appendizitis des Neugeborenen. Kindergrtzliche Praxis 289-292, 1975
BAX ET AL.
15. Sanchez EB: Appendicitis aguda en el prematuro. An Esp Pediatr 9:543-546, 1976 16. Fowkes GL: Neonatal appendicitis. Br Med J 1:997998, 1976 17. Touloukian R J, Posch JN, Spencer R: The pathogenesis of ischemic gastroenterocolitis of the neonate: Selective gut mucosal ischemia in asphyxiated neonatal piglets. J Pediatr Surg 7:194-205, 1972 18. Touloukian R J: Neonatal necrotizing enterocolitis. Surg Clin North Am 56:281-298, 1976 19. Joshi VV, Winston YE, Kay S: Neonatal necrotizing enterocolitis. Am J Dis Child 126:113-116, 1973 20. Martin LW, Perrin EV: Neonatal perforation of the appendix in association with Hirschsprung's disease. Ann Surg 166:799-802, 1967 21. G~istrin U, Josephson S: Appendiceal peritonitis and megacolon in the neonatal period. Acta Chit Scand 136:153155, 1970
p
ERFORATION o f t h e a p p e n d i x is r a r e in t h e n e w b o r n p e r i o d in c o n t r a s t w i t h its o c c u r r e n c e in l a t e r c h i l d h o o d . In 1966 F o n k a l s rud ~ r e v i e w e d 172 cases of n e o n a t a l peritonitis. O f t h e s e 172 cases 79 h a d peritonitis on a basis o f g a s t r o i n t e s t i n a l p e r f o r a t i o n , b u t in not one p a t i e n t was t h e p e r f o r a t i o n l o c a l i z e d in the a p p e n d i x . I d i o p a t h i c p r i m a r y p e r i t o n i t i s was d i a g n o s e d in 9 p a t i e n t s . In 1969 L l o y d 2 w r o t e on t h e e t i o l o g y of g a s t r o i n t e s t i n a l p e r f o r a t i o n s in t h e n e w b o r n , r e v i e w i n g 402 cases. A g a i n no m e n t i o n was m a d e of t h e a p p e n d i x as a site of p e r f o r a t i o n , w h i l e in 25 p a t i e n t s t h e site o f perfor a t i o n was not d e t e r m i n e d . S c h a u p p 3 r e p o r t e d on n e o n a t a l " a p p e n d i c i t i s " in 1960, d e s c r i b i n g 5 cases of his o w n a n d r e v i e w i n g 19 o t h e r s f r o m t h e l i t e r a t u r e . S i n c e 1960, h o w e v e r , at least 20 n e w cases of so-called n e o n a t a l " a p p e n d i c i t i s "
From the Departments o f Pediatric Surgery and Pediatrics, Sophia Children's Hospital and Neonatal Unit, Erasmus University, Rotterdam, The Netherlands. Address reprint requests to N. M. A. Bax, University Hospital Rotterdam, Sophia Children's Hospital and Neonatal Unit, Gordelweg 160, 3038 GE Rotterdam, The Netherlands. 9 1980 by Grune & Stratton, Inc. 00 22-3468/80/150 2~)016501.00/0
200
h a v e b e e n a d d e d to t h e world l i t e r a t u r e 4-~6 s e e m ingly i n d i c a t i n g an i n c r e a s i n g i n c i d e n c e of this problem. CASE REPORT
A female child, weighing 2420 g, was delivered at 35 wk gestation from a 25-yr-old mother. Pregnancy had been uneventful until the membranes ruptured spontaneously 84 hr before birth. No problems were encountered during delivery and the Apgar score was 8 at 1 min and 10 at 5 min. On the fourth day, the serum total bilirubin rose to 235 #mole/1 for which she received phototherapy and extra fluids in a peripheral vein. On the seventh day she developed a temperature of 39.9~ and became clinically ill with bile-stained vomiting, constipation, abdominal distension, grunting respiration, and poor peripheral circulation. Blood culture and lumbar puncture were done at this time, but no bacteria were cultured and direct microscopy, total protein and glucose content of cerebrospinal fluid were normal. She was started on kanamycin and cephaloridin intravenously, but her condition did not improve. On the 12th day of life she was referred to the Sophia Children's Hospital, Rotterdam. On admission she was clearly septic and presented with erythema and edema of the skin of the right iliac fossa where a mass could be felt. A diagnosis of peritonitis possibly secondary to necrotizing enterocolitis or appendicitis was made. A plain abdominal x-ray showed free air in the peritoneal cavity and signs of ascites. At laparotomy, diffuse purulent peritonitis was found, but without obvious perforation. A careful search revealed a small, apparently superficial, defect at the tip of the appendix, which otherwise looked healthy. It was decided to perform an appendectomy. During ligation of the base of the appendix feces extruded through the defect, confirming the diagnosis of appendiceal perforation. Escherichia coli and bacteroides were cultured from the peritoneal cavity. Both were sensitive for carbenicillin and gentamycin, which she had received in combination since admission to our hospital. She recovered without complications and was discharged in good health. Hirschsprung's disease was excluded by mucosal biopsy. Histologic examiniation of the removed appendix revealed the presence of periappendicitis without signs of classical appendicitis. DISCUSSION
W e believe t r u e a p p e n d i c i t i s as seen in o l d e r c h i l d r e n to be an e x c e e d i n g l y r a r e o c c u r r e n c e in t h e n e w b o r n . T h e t e r m i n o l o g y in t h e l i t e r a t u r e t e n d s to be c o n f u s i n g as m o s t c a s e s o f p e r f o r a tion of t h e a p p e n d i x in the n e o n a t a l period a r e classed t o g e t h e r u n d e r t h e t e r m " a p p e n d i c i t i s . "
Journal of Pediatric Surgery, Vol. 15, No. 2 (April), 1980
NEONATAL PERFORATION OF THE APPENDIX
201
We feel that many of these cases of neonatal "appendicitis" are the result of localized ischemic full thickness necrosis, a form of neonatal necrotizing enterocolitis. Animal experiments, working on the concept of selective circulatory shut-down as an asphyxial defence mechanism (the so-called diving reflex), demonstrate that bowel-wall perfusion and especially mucosal perfusion is dramatically reduced in the stomach, distal ileum and colon during asphyxia. ~7 We strongly suspect that the appendix participates in this process. As stated by Touloukian, ~8 localized perforation without obvious surrounding necrosis can exist and represents a very well localized full thickness zone of necrosis, particularly if found in the ileum or colon (or in the appendix). This is not surprising as the intestine with neonatal necrotizing enterocolitis has a marked healing capacity. ~9 The time that elapsed between the onset of neonatal necrotizing enterocolitis and the clinical manifestations of a perforation may have been long enough for the healing of the rest of the bowel without full thickness necrosis, so that at laparotomy only a localized perforation is seen, the rest of the bowel looking quite normal. We have found only one case in the literature where perforation of the appendix could have been associated with proximal appendiceal obstruction. ~3 In contrast, a calcified appendicolith is found in about one-third of the patients with classic appendicitis beyond the neonatal period. H,~3 Obstructive disease of the colon, e.g., Hirschsprung's disease, has been implicated in the pathogenesis of perforation of the appendix in the neonatal period. 2~ According to La Place's Law, however, obstruction of the distal colon is more likely to result in perforation of the cecum than of the remaining colon or appendix if mechanical causes alone are to be considered. We believe that the perforation of the appendix in such cases is the result of the accompanying
enterocolitis and not directly due to the mechanical effects. Perforation of the appendix in the neonatal period while still very rare, is being reported with increasing frequency. At the same time there has been an increase in the frequency of neonatal necrotizing enterocolitis. 18 It is remarkable that factors that have been implicated in the etiology and the pathogenesis of neonatal necrotizing enterocolitis, such as prematurity, perinatal asphyxia, premature rupture of membranes and umbilical vessel catherization, are precisely those which have been reported in most of the cases of neonatal "appendicitis." The age of onset of the symptoms is also similar in both. Further support for the theory that neonatal "appendicitis" is a separate disease entity from appendicitis in later childhood, is the extreme rarity of reports of appendicitis in babies between the ages of one month and one year. Of the combined group of 72 patients with appendicitis under the age of 2 yr, reported by Barlett 11 and Grosfeld, 13 only 7 patients fell in the age group of between 1 and 12 mo and only 1 patient out of 30 patients reported by Fields 8 was under 3 yr of age. We feel therefore, that the case presented here and many of the cases of neonatal "appendicitis" reported in the literature, are examples of neonatal necrotizing enterocolitis. One of the three patients described by Grosfeld 13 had the typical changes of necrotizing enterocolitis of the cecum and appendix. Furthermore, we suggest that a similar process situated in the appendix or elsewhere in the bowel may lead to the so-called idiopathic primary peritonitis. We should like to stress the importance of a thorough search for such localized defects before closing the abdomen with this diagnosis. Failure to find and to deal with the site of perforation would explain the very high mortality reported in babies in whom idiopathic primary peritonitis has been diagnosed.
REFERENCES 1. Fonkalsrud EW, Ellis DG, Clatworthy HW: Neonatal peritonitis. J Pediatr Surg 1:227-239, 1966 2. Lloyd JR: The etiology of gastrointestinal perforations in the newborn. J Pediatr Surg 4:77-85, 1969 3. Schaupp W, Clausen EG, Ferrier PK: Appendicitis during the first month of life. Surgery 48:805-811, 1960
4. Hardman RP, Bowerman D: Appendicitis in the newborn. Am J Dis Child 105:99 101, 1963 5. Firror HV, Myers HAP: Perforating appendicitis in premature infants. Surgery 56:581-583, 1964 6. Neve R, Quenville NF: Appendicitis with perforation in a 12 day-old infant. Can Med Assoc J 94:447-448, 1966
202
7. Tabrinsky J, Westerfeld R, Cavanaugh J: Appendicitis in the newborn. Am J Dis Child 3:557 558, 1966 8. Fields IA, Cole NM: Acute appendicitis in infants thirty-six months of age or younger. Am J Surg 113:269275, 1967 9. Denes J, Gergely K, Mohacsi A, Leb J: Die frfihgeborenen-appendicitis. Z Kinderchir 5:400-406, 1968 10. Parsons JM, Miscall BG, McSherry CK: Appendicitis in the newborn infant. Surgery 67:841-843, 1969 11. Barlett RH, Eraklis A J, Wilkinson RH: Appendicitis in infancy. Surg Gynecol Obstet 130:99-104, 1970 12. Schellerer W, Schwemme K, Decker R: Perforierte Appendizitis bei einem FrUhgeborenen im Alter von 14 Tagen. Z Kinderchir 9:434-437, 1971 13. Grosfeld JL, Weinberger M, Clatworthy HW: Acute appendicitis in the first two years of life. J Pediatr Surg 8:285-293, 1973 14. Reuter G, Krause l: Beitrag zur Problematik der Appendizitis des Neugeborenen. Kindergrtzliche Praxis 289-292, 1975
BAX ET AL.
15. Sanchez EB: Appendicitis aguda en el prematuro. An Esp Pediatr 9:543-546, 1976 16. Fowkes GL: Neonatal appendicitis. Br Med J 1:997998, 1976 17. Touloukian R J, Posch JN, Spencer R: The pathogenesis of ischemic gastroenterocolitis of the neonate: Selective gut mucosal ischemia in asphyxiated neonatal piglets. J Pediatr Surg 7:194-205, 1972 18. Touloukian R J: Neonatal necrotizing enterocolitis. Surg Clin North Am 56:281-298, 1976 19. Joshi VV, Winston YE, Kay S: Neonatal necrotizing enterocolitis. Am J Dis Child 126:113-116, 1973 20. Martin LW, Perrin EV: Neonatal perforation of the appendix in association with Hirschsprung's disease. Ann Surg 166:799-802, 1967 21. G~istrin U, Josephson S: Appendiceal peritonitis and megacolon in the neonatal period. Acta Chit Scand 136:153155, 1970